| RRC ID |
30710
|
| Author |
Nagashima H, Okuyama Y, Asao A, Kawabe T, Yamaki S, Nakano H, Croft M, Ishii N, So T.
|
| Title |
The adaptor TRAF5 limits the differentiation of inflammatory CD4(+) T cells by antagonizing signaling via the receptor for IL-6.
|
| Journal |
Nat Immunol
|
| Abstract |
The physiological functions of members of the tumor-necrosis factor (TNF) receptor (TNFR)-associated factor (TRAF) family in T cell immunity are not well understood. We found that in the presence of interleukin 6 (IL-6), naive TRAF5-deficient CD4(+) T cells showed an enhanced ability to differentiate into the TH17 subset of helper T cells. Accordingly, TH17 cell-associated experimental autoimmune encephalomyelitis (EAE) was greatly exaggerated in Traf5(-/-) mice. Although it is normally linked with TNFR signaling pathways, TRAF5 constitutively associated with a cytoplasmic region in the signal-transducing receptor gp130 that overlaps with the binding site for the transcription activator STAT3 and suppressed the recruitment and activation of STAT3 in response to IL-6. Our results identify TRAF5 as a negative regulator of the IL-6 receptor signaling pathway that limits the induction of proinflammatory CD4(+) T cells that require IL-6 for their development.
|
| Volume |
15(5)
|
| Pages |
449-56
|
| Published |
2014-5-1
|
| DOI |
10.1038/ni.2863
|
| PII |
ni.2863
|
| Description |
HEK293T細胞に発現させ、IL6刺激によって引き起こされるSTAT3とIL6シグナル受容体gp130との結合、さらにTRAF5による阻害を調べるために使用されました。
|
| PMID |
24681564
|
| PMC |
PMC4108451
|
| MeSH |
Animals
CD4 Antigens / metabolism
Cell Differentiation / genetics
Cells, Cultured
Cytokine Receptor gp130 / metabolism*
Disease Progression
Encephalomyelitis, Autoimmune, Experimental / immunology*
Interleukin-6 / immunology
Mice
Mice, Inbred Strains
Mice, Knockout
Myelin-Oligodendrocyte Glycoprotein / immunology
Peptide Fragments / immunology
STAT3 Transcription Factor / metabolism
Signal Transduction / genetics
T-Lymphocyte Subsets / immunology*
TNF Receptor-Associated Factor 5 / genetics
TNF Receptor-Associated Factor 5 / metabolism*
Th17 Cells / immunology*
Transcriptional Activation / genetics
|
| IF |
20.479
|
| Times Cited |
24
|
|
WOS Category
|
IMMUNOLOGY
|
| Resource |
| DNA material |
pEF-Flag-mSTAT3 (wild) (RDB02353). |
